3-(2-Fluorophenyl)-5-(4-oxopiperidin-1-yl)-[1,2,3]triazolo[1,5-a]quinazoline → 3-(2-Fluorophenyl)-5-(4-hydroxy-4-methylpiperidin-1-yl)-[1,2,3]triazolo[1,5-a]quinazoline

HRID 1581632Notes

Reaction equation

HRID 1581632 reaction equation
[CH3:1][Mg]Br.[F:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[C:11]1[N:12]=[N:13][N:14]2[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[C:17]([N:24]3[CH2:29][CH2:28][C:27](=[O:30])[CH2:26][CH2:25]3)=[N:16][C:15]=12>O1CCCC1.O.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>[F:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[C:11]1[N:12]=[N:13][N:14]2[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[C:17]([N:24]3[CH2:25][CH2:26][C:27]([OH:30])([CH3:1])[CH2:28][CH2:29]3)=[N:16][C:15]=12

Participants

6

Reactant 2

HCID 99251083-(2-Fluorophenyl)-5-(4-oxopiperidin-1-yl)-[1,2,3]triazolo[1,5-a]quinazolineHCID 178418573HCID 178418573, compound

Product 1

HCID 101341923-(2-Fluorophenyl)-5-(4-hydroxy-4-methylpiperidin-1-yl)-[1,2,3]triazolo[1,5-a]quinazolineYield 47%

Reagents, catalysts & solvents 3

HCID 311Citric AcidSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Methylmagnesium bromide (3M in diethyl ether, 0.24 ml, 0.72 mmol) was added to a stirred solution of 3-(2-fluorophenyl)-5-(4-oxopiperidin-1-yl)-[1,2,3]triazolo[1,5-α]quinazoline (Example 22) (0.107 g, 0.3 mmol) in dry tetrahydrofuran (2 ml) at room temperature under nitrogen. After stirring for 2 h, the mixture was diluted with water (20 ml) and 1M aqueous citric acid (5 ml). The mixture was extracted with dichloromethane (20 ml) and the organic extract was dried (Na2SO4), filtered and concentrated. Preparative thin layer chromatography on silica, eluting with 2% methanol:dichloromethane, gave 3-(2-fluorophenyl)-5-(4-hydroxy-4-methylpiperidin-1-yl)-[1,2,3]triazolo[1,5-α]quinazoline (0.053 g, 47%). δH (360 MHz; CDCl3) 1.38 (3H, s), 1.75-1.85 (2H, m), 1.90-2.00 (2H, m), 3.56-3.64 (2H, m), 3.83-3.89 (2H, m), 7.20-7.30 (2H, m), 7.30-7.40 (1H, m), 7.60 (1H, dd, J=7 and 7), 7.88 (1H, dd, J=7 and 7), 8.02 (1H, d, J=7), 8.15 (1H, dd, J=7 and 7), 8.68 (1H, d, J=7); m/z (ES+) 378 (M+H+).

Workup

  1. extractionThe mixture was extracted with dichloromethane (20 ml)
  2. extractionthe organic extract
  3. dry with materialwas dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. washPreparative thin layer chromatography on silica, eluting with 2% methanol

Sources & evidence

ORD record
ord-2eaaeba0e0f5418885ea0c1db43c7f89
Source dataset
uspto-grants-2004_05
Patent number
US06730681B2

Reaction notes

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